1. IL-17A induces pro-inflammatory cytokines production in macrophages via MAPKinases, NF-κB and AP-1.
- Author
-
Chen J, Liao MY, Gao XL, Zhong Q, Tang TT, Yu X, Liao YH, and Cheng X
- Subjects
- Animals, Cell Line, Cytokines genetics, Enzyme Inhibitors pharmacology, Interleukin-17 metabolism, Interleukin-1beta genetics, Interleukin-6 genetics, Macrophages drug effects, Mice, Phosphorylation drug effects, Protein Kinase Inhibitors pharmacology, Receptors, Interleukin-17 metabolism, Tumor Necrosis Factor-alpha genetics, p38 Mitogen-Activated Protein Kinases antagonists & inhibitors, p38 Mitogen-Activated Protein Kinases metabolism, Cytokines metabolism, Inflammation metabolism, Interleukin-17 pharmacology, Macrophages metabolism, Mitogen-Activated Protein Kinases metabolism, NF-kappa B metabolism, Transcription Factor AP-1 metabolism
- Abstract
Background: Interleukin (IL)-17A, a newly identified cytokine, may participate in the transition of a stable plaque into an unstable plaque. Macrophages play a critical role in the destabilization of atherosclerotic plaque., Methods: RAW 264.7 cells were stimulated with IL-17A. The mRNA expression of inflammatory cytokines was determined by RT-PCR. The cytokines production in the supernatants was measured by ELISA. Small interfering RNA (siRNA) was used to confirm that IL-17A-induced pro-inflammatory cytokines production via IL-17RA signaling. The western blot assay was used to detect the phosphorylation of MAPKinases including p38 and ERK1/2. The DNA binding activity of nuclear factor NF-κB and AP-1 were detected by EMSA., Results: IL-17A induced the production of pro-inflammatory cytokines in macrophages in a time- and dose-dependent manner, such as tumor necrosis factor (TNF)-α, IL-1β, and IL-6. Meanwhile, IL-17A resulted in the phosphorylation of p38 and ERK1/2 and increased DNA-binding activity of NF-κB and AP-1. Pharmacological inhibitors of p38 and ERK1/2 partly attenuated IL-17A-induced TNF-α, IL-1β, and IL-6 production. Either NF-κB inhibitor or AP-1 inhibitor also partly decreased the IL-17A-induced cytokine production., Conclusions: IL-17A induces pro-inflammatory cytokines production in macrophages via MAPKinases, NF-κB and AP-1 pathway., (© 2013 S. Karger AG, Basel.)
- Published
- 2013
- Full Text
- View/download PDF